BMS2002 - membrane transport and ion channels Flashcards
protein classes in the plasma membrane
transporters, linkers, receptors, enzymes
types of membrane transporters
channel protein
carrier protein
pump
passive transport
along concentration gradient
no ATP hydrolysis
3 main types of passive transport
simple diffusion
osmosis
facilitated diffusion
active transport
movement against concentration
energy expended - ATP
2 main types of active transport
- primary/direct - directly uses ATP
- secondary/indirect - couples with another molecule moving along electrochemical gradient
Na+/K+ ATPase
Na+ in cytoplasm binds pump
pump is phosphorylated by ATP
conformational change -> NA+ release
EC K+ binds pump -> dephosphorylation
pump returns to original conformation
K+ is released from the pump
3 ways of gating ion channels
voltage-gated
ligand-gated
tension-gated
flux
movement, occurs due to concentration across the membrane
mammalian Vm
~55mV
resting membrane potential maintained by….
sodium potassium pump
equilibrium potential is when
ion flux in = ion flux out
what to look for when investigating ion channel structure
- biochemical properties of specific aa side chains -> predict protein structures
- hydrophobic = transmembrane region
- polar/charged/hydrophobic = extramembrane, ligand binding
experimental ways of investigating ion channel structure
X-ray crystallography - standard
Electron microscopy - emerging
characteristics of ion channels
- can be difficult to crystalise
- transmembrane
- large proteins
- multiple conformations
- multiple subunits
- dynamic and disordered
- not very stable
ion channel structure
multiple alpha subunits - typical potassium channel has 4 = tetramer
4 stages of an action potential
- resting phase
- depolarisation
- repolarisation
- hyperpolarisation (Refractory)
absolute refractory period
- membrane cannot generate another action potential
- sodium channels are inactivated
relative refractory period
- membrane could generate another action potential if given a larger than normal stimulus
- VG sodium channels are recovered
- VG potassium channels are still open
movement of action potential down an axon
travels via current loops
- nearby area becomes depolarised by the current AP to initate the next AP
channelopathy
pathology or disease arising from ion channel dysfunction
3 pain mechanisms
- noiciceptive - temperature, acid, etc
- inflammatory - immune
- neuropathic - nervous
pathway of noxiuos stimuli
noxious stimuli -> peripheral terminals of specific unmyelinated C-fibre and thinly myelinated Ad fibre -> spinal cord -> central pathways -> cortex -> pain is experienced
options for neuropathic pain treatment
TCAs, anticonvulsants, Na+ channel blockers, NMDA receptor antagonists, opiods
4 therapeutic strategies for pain
INHIBIT the ion channel that:
1. senses the stimuli/initiates the AP
2. propagates the AP
3. are involved in DRG neurotransmission
4. process stimuli centrally within the brain
Primary Erthromelagia (PEM)
autdom mutation in SCN9A
- bilateral burning and redness in hands and feet
- attacks triggered by exersize / heat
mutation -> shift in hyperpolarizing direction -> reduced threshold -> increased excitability
-> increased symptom severity
Paroxysmal extreme pain disorder
autdom mutation in SCN9A
- severe pain in rectal/ocular/mandibular areas
- triggered by chewing/heat
- mutation -> incomplete channel activation
- treated with carbamazepine
Complete insensitivity to pain (CIP)
autres mutation in SCN9A
- loss of all pain sensation
- nonsense mutations -> truncated proteins
- often suffer major injuries as a result
